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Pain: killing it safely

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Chronic pain is a devastating health problem that affects millions of peoplearound the world

Chronic pain is a devastating health problem that affects millions of people around the world. In the UK alone, nearly eight million people are living with moderate-to-severe pain lasting for more than six months-and the figures are on the rise. In his annual report published in March this year, Professor Sir Liam Donaldson, the UK government's Chief Medical Officer, revealed that chronic pain is two to three times more common now than it was 40 years ago. Currently, over a third of UK households have someone in pain at any given time. Unlike acute pain, which warns us of actual or potential harm to the body, chronic pain serves no useful purpose and, yet, has a major impact on people's lives. Indeed, 65 per cent of sufferers report difficulty sleeping, and nearly 50 per cent report having problems with social activities, walk-ing, driving or having a normal sex life. Depression is also common, affecting about half of all chronic-pain patients. For some sufferers, suicide appears to be the only solution. But it doesn't have to be that way. New evidence suggests that chronic pain may simply be due to an un-recognized nutritional deficiency or some other sort of imbalance in the body. An holistic approach that views pain in a very different way from conventional medicine may be the closest we've come to a cure.

Conventional pain treatment

Chronic pain is a complex condition with many different causes-and sometimes no known cause at all-yet conventional medicine's answer is generally the same: to treat it with pain-relieving drugs. Paracetamol (acetaminophen) is thought to reduce pain by inter-rupting or suppressing pain signals carried along the nerves, while opioids-which are much stronger drugs-affect the way in which pain is processed in the brain and spinal cord to reduce the sensation of pain. Anti-inflammatory drugs tackle pain by reducing inflammation. But while these drugs may work in theory, in practice, they're failing to hit the spot. According to a study of UK nursing homes, cited in Sir Liam Donaldson's annual report, most residents experienced constant or frequent moderate-to-severe pain, despite the fact that 99 per cent were on pain medication. In another study of chronic-pain patients of all ages, over one-third reported inadequate pain control, and more than two-thirds admitted that, at times, their medication failed completely. Opioids such as morphine, oxyco-done, buprenorphine and fentanyl have long been regarded as among the most effective drugs for the treatment of pain, but even these have proved useless in many cases. In a review of 15 trials of opioids for chronic non-malignant pain (CNMP), the average reduction in pain intensity was only around 30 per cent, and the dropout rate was 56 per cent after two years. Moreover, only three of eight studies that assessed functional disturbance (such as being unable to work because of pain) found any improvement with opioid agents (Pain, 2004; 112: 372-80). A number of other reviews of the use of opioids for chronic pain have similarly reported only modest evidence of efficacy with these drugs. What's more, although the medical use of opioids has increased over the years, there is no evidence that this has resulted in a lower prevalence of chronic pain. In Denmark, for example, the use of opioids for CNMP has risen by more than 600 per cent over the past two decades. Yet, in a national survey, 90 per cent of opioid users continued to complain of moderate to very-severe pain compared with 46 per cent of non-opioid users (Exp Clin Psychopharmacol, 2008; 16: 405-16). Worse, in addition to being largely inadequate, another problem with conventional painkillers is their side-effects (see box, page 7). Clearly, these drugs are not the answer to the problem of pain. The good news for pain sufferers, however, is that the failings of mod-ern medicine have encouraged studies into alternative methods for treating pain. Now, there's a wide variety of non-drug therapies that offer new hope to sufferers.

The vitamin D approach

So far, some of the most compelling evidence suggests that the solution to chronic pain could be something as simple as vitamin D. In a nationwide UK study of nearly 7000 adults, scientists at the Institute of Child Health in London found a link between low levels of vitamin D and chronic wide-spread pain (CWP). Although the findings were not significant in men, in women, CWP prevalence varied according to vitamin D concentrations. Those with levels of 75-99 nmol/L-the range deemed necessary for bone health-had the lowest rates of CWP, which were just over 8 per cent. In contrast, in women with levels less than 25 nmol/L, CWP rates were nearly doubled at 14.4 per cent (Ann Rheum Dis, 2009; 68: 817-22). Similar results were reported last year in an American study. Mayo Clinic researchers found a connection between inadequate vitamin D levels and the amount of opioid medication taken by patients suffering from chronic pain. Those with low vitamin D levels were taking much higher doses of medication-nearly twice as much-as those with adequate levels. Moreover, the low-vitamin-D opioid users reported poorer physical functioning and a worse overall perception of health (Pain Med, 2008; 9: 979-84). Although these two studies aren't proof that a lack of vitamin D causes chronic pain, they do contribute to a growing body of evidence suggesting an important role for this vitamin in pain control. Indeed, according to an extensive review of the research so far-published online at Pain Treat-ment Topics (http://paintopics.org/ pdf/vitamind-report.pdf)-having not enough vitamin D is linked to a raft of painful maladies, including bone and joint pain, muscle aches, fibro-myalgia, rheumatic disorders, osteo-arthritis and other complaints. Much of the research has focused on chronic musculoskeletal-related pain. Indeed, the report's author, Dr Stewart Leavitt, identified 22 clinical studies investigating vitamin D status in patients with this sort of pain. Across these studies, an average of around 70 per cent of patients with chronic musculoskeletal pain were found to be deficient in vitamin D. The evidence also shows that supplementing with vitamin D can dramatically improve pain. In 324 women with chronic back pain, vitamin D eased symptoms in 95 per cent-and in 100-per-cent of those with the most severe D deficiency (Spine [Phila Pa 1976], 2003; 28: 177-9). According to Leavitt, vitamin D deficiency might lead to musculo-skeletal pain by causing hypocalcae-mia-low levels of circulating calcium-which "sets in motion a cascade of biochemical reactions negatively affecting bone metabolism and health". One of these reactions is an increase in parathyroid hormone (PTH), which impairs bone mineraliz-ation, causing a spongy bone matrix to form. As this matrix absorbs fluid, the resultant expanding pressure triggers pain in the tissues overlying the bones that are abundant in sensory pain fibres. In addition, vitamin D deficiency might contribute to pain in other ways. Several studies cited in Leavitt's report found that vitamin D may be involved in non-musculoskeletal pain syndromes, including neuropathy, migraine headaches and inflammatory autoimmune conditions such as inflammatory bowel disease. Whatever the mechanism involved, the data suggest that checking for vitamin D deficiency-and correcting it (see box, page 8)-may be a key factor in chronic-pain management.

Mind-body techniques

Observing soldiers during World War II proved that the mind plays a huge part in the perception of pain. Among soldiers with equally devastating wounds, some asked for less morphine than others. Their perception of the wound and what it meant in their lives appeared to be crucial. To one, the wound meant surviving the battle and going home; to another, it meant major surgery and a lower income, fewer activities and other negative consequences (Purves D et al., eds. Neuroscience, 2nd edn. Sunderland, MA: Sinauer Associates, 2001). Nowadays, when considering treat-ment for chronic pain, it's accepted that the emotional reaction to pain is almost as important as the sensation itself in determining how well the patient will cope. This means that therapies that take this mind-body connection into account are partic-ularly useful for managing pain. One such therapy is hypnosis, a technique that introduces instruc-tions or suggestions to bring about changes in subjective experience, perception, sensation, emotion, thoughts and behaviour. In the case of chronic pain, hypnosis enables patients to control the intensity of the pain, to manage the pain and the emotions accompanying it, and to find suitable resources to deal with it, thereby allowing them to be involved in their own treatment (Rev Med Suisse, 2009; 5: 1380-2, 1384-5). Scientific reviews-called 'meta-analyses', as they analyze all of the findings and assess them altogether-have found hypnosis to be effective for chronic pain. On combining 18 studies of laboratory-induced and patients' pain, the findings were that hypnosis obtained greater pain relief than in 75 per cent of those given either the usual care or no treatment at all (Int J Clin Exp Hypn, 2000; 48: 138-53). In yet another meta-analysis of the efficacy of hypnosis for headache, lower-back, temporomandibular joint (TMJ), cancer-related and sickle-cell-disease pain, as well as the pain related to fibromyalgia, osteoarthritis and disability, hypnotherapy resulted in greater pain reduction than either standard care or no treatment. The authors concluded that ". . . hypnotic treatment for chronic pain results in significant reductions in perceived pain that maintain for at least several months, and possibly longer" (J Rehabil Res Dev, 2007; 44: 195-222). As well as working, a further bonus of hypnosis is that it is almost always a benign treatment with little risk of negative side-effects. Indeed, what 'side-effects' do occur are overwhelm-ingly positive, including a greater sense of control over pain, greater overall feelings of wellbeing, and less tension, stress and anxiety (J Rehabil Res Dev, 2007; 44: 195-222). Another mind-body technique with a good track record for pain control is biofeedback, a process of recording and feeding back real-time informa-tion on how the body is functioning to allow the patient to learn how to actively control these functions. Numerous studies have established that biofeedback is an effective treatment for a wide range of chronic pain problems, including migraine and tension-type headaches, muscle-related orofacial pain, lower-back pain, phantom-limb pain and fibro-myalgia. The technique generally works because it first identifies the patient's own, individual physiological dysfunction that is causing the pain, and then helps the patient to recognize when this dysfunction is occurring and to correct it using various strategies. This means of getting to the root of the pain may be why a number of studies have found biofeedback to be more effective than conventional treatments for chronic pain (J Rehabil Res Dev, 2007; 44: 195-222). Other techniques that integrate the body and mind have also proved useful for chronic pain. Yoga and mindfulness meditation are especially effective for treating chronic lower-back pain (J Altern Complement Med, 2008; 14: 637-44; J Pain, 2008; 9: 841-8), while guided imagery-which uses mental images to imagine and 'create' the desired physical outcome-has shown promise in alleviating the pain of osteoarthritis and fibromyalgia (Fam Community Health, 2008; 31: 204-12; Pain Med, 2007; 8: 359-75).

Energy medicine

Besides mind-body techniques, another drug-free approach that's proved to be successful among pain patients is the use of so-called 'energy medicine'. According to the US National Cen-ter for Complementary and Alternative Medicine (NCCAM), this comes in two types: the first includes bio-electromagnetic-based therapies that involve electromagnetic fields (EMFs) such as pulsed fields, magnetic fields and alternating-/direct-current fields; while the second includes biofield therapies that are intended to affect the energy fields that are thought to surround and penetrate the human body (J Rehabil Res Dev, 2007; 44: 195-222). Both types of energy medicine have proved to be beneficial for chronic pain, but one of the most popular therapies-which falls into the first energy-medicine category-is transcutaneous electrical nerve stimulation, or TENS. This technique transmits electrical impulses into the body through electrodes that are placed on or near the painful area. Although it doesn't address the underlying cause of pain, these electrical impulses produce a tingling sensation that reduces the pain itself. Indeed, numerous studies have shown that TENS works for a range of chronic-pain conditions-from musculo-skeletal pain, such as back and neck pain, to the persistent pain that often follows surgery (Pain, 2007; 130: 157-65; Curr Opin Anaesthesiol, 2009; Jul 9: Epub ahead of print). Of the other bioelectromagnetic-based therapies that are currently available, pulsed electromagnetic field (PEMF) generators and cranial electrotherapy stimulation (CES) hold particular promise for patients who suffer from chronic pain. PEMF generators-which include low-power, wearable devices designed for virtually continuous use as well as high-power machines meant to be used several times a day-are able to help osteoarthritis sufferers, and can reduce chronic migraine headache activity by around 80 per cent (J Rehabil Res Dev, 2007; 44: 195-222). CES, which delivers a low-level electrical current through electrodes attached to the skin surface (usually on the ears), has proved to be better than a sham procedure for treating fibromyalgia pain as well as the pain associated with spinal-cord injury (J Clin Rheumatol, 2001; 7: 72-8; J Rehabil Res Dev, 2006; 43: 461-74). Precisely how these two electrical treatments work is still not fully understood. PEMF generators appear to increase blood flow to the areas exposed to the EMFs, whereas CES is thought to bring about changes in certain chemicals of the brain, including serotonin and norepineph-rine. Both mechanisms appear to have a positive affect on pain (J Rehabil Res Dev, 2007; 44: 195-222). As for biofield therapies, the other type of energy medicine, acupuncture is the one that is most extensively studied. As with other biofield modalities, this traditional Chinese medical technique is based on the concept that all living things, including humans, are infused with a subtle form of energy (qi), and that any disturbances to this energy result in illness. This means that acupuncture treats pain and other conditions by improving the quality, balance and flow of energy within the body. In fact, acupuncture appears to be especially effective for back pain. In a meta-analysis of 33 randomized, controlled trials, acupuncture was superior to sham acupuncture for relieving chronic lower-back pain. However, one drawback is that the study was only looking at short-term results (Ann Intern Med, 2005; 142: 651-63). More recent studies suggest that acupuncture might also help those who have shoulder pain, headaches, TMJ dysfunction, fibromyalgia, osteoarthritis of the knee, tennis/golfer's elbow and other painful conditions (J Altern Complement Med, 2009; 15: 613-8; MMW Fortschr Med, 2007; 149: 37-9). Nevertheless, more studies are needed to determine whether the pain relief with acupuncture is long-lasting (Anesth Analg, 2008; 106: 611-21). Other biofield therapies, including Qigong, Reiki and Therapeutic Touch, have been used to treat pain. The evidence for Qigong is the most encouraging, with one study rating its level of efficacy, on the basis of the research so far, as 2-3 out of 5, which means that it's 'possibly' to 'probably' effective for the treatment of chronic pain (J Rehabil Res Dev, 2007; 44: 195-222). Like acupuncture, Qigong is a traditional technique for enhancing the flow of qi in the body through combining movement, meditation and breath regulation. For pain control, 'Qi therapy' was particularly successful in reducing negative psychological symptoms, while boosting melatonin and immune-system activity-at least in younger subjects. Nevertheless, in a study of 94 elderly patients, those who received Qi therapy had less pain-and less anxiety, depression and fatigue-compared with those given sham therapy as a control (Complement Ther Med, 2003; 11: 159-64). In a systematic review of all randomized clinical trials (up to January 2007) assessing Qi therapy for chronic pain, Qigong produced greater reductions in pain than did the control treatments. Moreover, a meta-analysis of two studies showed a significant effect of Qi therapy compared with general care for treating chronic pain (J Pain, 2007; 8: 827-31).

Manipulation-based medicine

Yet another approach to pain management is the use of manipulative and body-based techniques such as chiro-practic and massage therapy. These methods focus on physiological structures and systems, including the bones and joints, soft tissues, and the circulatory and lymphatic systems. They can be particularly effective for chronic pain, as practitioners of these therapies generally tailor their treatments to the specific needs of each individual patient. Chiropractic manipulation-specifically, spinal manipulation therapy (SMT)-is the treatment of choice for many chronic back-pain patients. Studies show that it has clinically and statistically significant benefits com-pared with either sham manipulations or treatments considered to be ineffective or even harmful, such as bed rest and traction (Cochrane Database Syst Rev, 2004; 1: CD000447). SMT has also been used in the treatment of a variety of other painful conditions, including fibromyalgia, carpal tunnel syndrome, migraine and dysmenorrhoea (menstrual pain), and was found to be more effective than conventional treatments in improving pain and disability (J Rehabil Res Dev, 2007; 44: 195-222). Massage therapy for chronic pain also has plenty of supporting evidence. In a recent comprehensive review by the prestigious Cochrane Collabora-tion, massage proved to be superior to joint mobilization, relaxation therapy, physical therapy, acupuncture and self-care education for the treatment of lower-back pain. What's more, the beneficial effects lasted for at least a year beyond the end of the treatment (Cochrane Database Syst Rev, 2008; 4: CD001929). In another study of patients with mixed chronic pain, massage therapy was at least as effective as the standard medical care. However, after three months, only those in the massage group still showed significant improvement (J Altern Complement Med, 2003; 9: 837-46). Interestingly, massage appears to have an impact on the brain that may explain its painkilling effects. It may be that massage raises levels of serotonin, which is thought to modulate the body's pain-control system. Another possibility is that massage promotes deep, restorative sleep, which reduces levels of sub-stance P, a brain chemical associated with pain (J Rehabil Res Dev, 2007; 44: 195-222).

Pain: a new paradigm

These therapies are merely a selection of the vast array of non-drug options currently available for chronic pain, and the search for alternative options continues to flourish. A major step forward is the realization that pain is not always the result of a mechanical breakdown or traumatic physical injury, but may be the result of a bio-chemical or energetic imbalance-or even an emotional one. If so, then the cure for chronic pain is unlikely to be found by popping the usual pills. Joanna Evans

Dangerous drug side-effects

Opioids are known to cause constipation, nausea and vomiting, sedation, cognitive impairment and respiratory depression. Worse, patients can develop a tolerance to the drug effects, resulting in physical dependence and withdrawal symptoms on stopping the medication. Estimated addiction rates among patients with non-cancer-related pain range from 3 per cent to almost 20 per cent (Drugs, 2003; 63: 17-32). Another class of drugs with a worrying safety profile are the non-steroidal anti-inflammatory drugs, or NSAIDs, which are commonly prescribed for arthritis, headache and other inflammatory conditions. In the US alone, some 60 million NSAID prescriptions are written each year. The main concern is the risk of gastrointestinal (GI) complications such as ulceration, perforation and bleeding. Indeed, the US drugs regulator, the Food and Drug Administration (FDA), has estimated that 2-4 per cent of the Americans who take these drugs for a year will develop one of these complications, leading to 107,000 hospitalizations and at least 16,500 deaths annually among arthritis patients alone (Am J Med, 1998; 105: 31S-8S; Geriatr Nurs, 2001; 22: 118-9). Recent evidence has also linked NSAIDs to serious cardiovascular events, including heart attack, angina and transient ischaemic attacks (TIAs, or 'mini-strokes') (Am J Cardiol, 2009; 103: 1227-37; Clin Ther, 2006; 28: 1827-36). Even good old aspirin-one of the less potent NSAIDs-has been associated with major risks of bleeding such as haemorrhagic stroke, a type of stroke caused by ruptured blood vessels leaking blood into the brain (Lancet, 2009; 373: 1849-60).

Nutrients for chronic pain

- Vitamin D. Sunlight is the best source of this vitamin but, as most of us don't get enough of it this way, pain expert Stewart Leavitt recommends (with the supervision of a qualified practitioner) a daily supplement of 2000 IU of vitamin D3 (cholecalciferol), along with a daily multivitamin that includes calcium and 400-800 IU of vitamin D. It may take up to nine months to experience the maximum effects of this regimen. - Glucosamine and chrondroitin sulphate. This combination is known to be effective for inflammatory conditions such as osteoarthritis of the knee (J Rehabil Res Dev, 2007; 44: 195-222). - Proteolytic enzymes, such as bromelain, have various pain-relieving properties that have proved useful in the treatment of rheumatic diseases (Wien Med Wochenschr, 1999; 149: 577-80). - Amino acids, such as d-phenylalanine and l-tryptophan, appear to increase pain tolerance in animals as well as in humans (Prog Clin Biol Res, 1985; 192: 363-70; J Psychiatr Res, 1982-1983; 17: 181-6).

Herbal painkillers

- Capsaicin, an extract of cayenne pepper, can ease many types of chronic pain when regularly applied to the skin. In one study, a capsaicin plaster was significantly better than a placebo in patients with chronic back pain (Arzneimittelforschung, 2001; 51: 896-903). - Ginger appears to have both analgesic and anti-inflammatory effects (J Ethnopharmacol, 2005; 96: 207-10). In a trial of women with menstrual pain, ginger supplements were just as effective as the NSAIDs mefenamic acid and ibuprofen in providing relief (J Altern Complement Med, 2009; Feb 13: Epub ahead of print). - Devil's claw (Harpagophytum procumbens) may be useful against arthritic and lower-back pain. According to one study, for the herb to be effective, the daily dose needs to provide at least 50 mg of the active ingredient harpagoside (Orthopade, 2004; 33: 804-8). - Willow bark (Salix alba), which is chemically related to aspirin, appears to provide acute, short-term relief for patients with lower-back pain (Cochrane Database Syst Rev, 2006; 2: CD004504).